Gonadotropin releasing hormone (GnRH) is synthesized/secreted from hypothalamic neurons and plays an integral role in normal reproductive function. Unlike most other neurons, the GnRH neurons are born in the olfactory placode and migrate into the hypothalamus during development. Although migratory failure clearly results in infertility, the molecular mechanisms that modulate GnRH neuronal migration in vivo are largely unknown. Recent studies from our laboratory suggest that adhesion related kinase (Ark) is expressed in GnRH neurons and may regulate GnRH neuronal adhesion, migration and gene expression. In the proposed studies, GnRH producing neuronal cell lines will be utilized to dissect Ark's role in these events. The signal transduction pathways required for Ark repression of GnRH promoter activity and the nuclear factors mediating this process will be defined. Aggregation and Boyden Chamber assays will be performed to evaluate whether Ark regulates GnRH neuronal cell adhesion and/or migration. Together, these studies will shed light on the molecular mechanisms governing GnRH neuronal gene expression and migration during development.